Anxiety Disorders are the most common mental illness in the US. Currently it is believed that many of these disorders are be triggered by environmental factors, but a predisposition to the disorder is strongly controlled by genetics factors. The ability to identify novel anxiety susceptibility genes in humans has been limited in part by the absence of endophenotypes for anxiety, and by the complexity of the constellation of diseases that comprise anxiety disorders. Since anxiety and fear represent ancient and evolutionarily conserved emotional states, animal models should be extremely valuable in dissecting the underlying neurobiology of anxiety and for identifying candidate genes. Simple animal models will allow for the identification of "core" anxiety responses that have since expanded and multiplied through evolution. A core anxiety response would also illuminate possible endophenotypes for anxiety disorders. The proposed experiments will identify novel behavioral responses to anxiogenic stimuli in Drosophila melanogaster. In these experiments the animals will be subjected to innately and conditionally aversive stimuli, and their responses in three behavioral measures will be determined. Drosophila is an extremely powerful genetic model system for the dissection of the behavioral and neurogenetic underpinnings of anxiety-like responses. Ultimately, the knowledge gained on these responses in this simple and agile genetic model system will permit the development of new and more detailed hypothesis on how different forms of anxiety may have evolved, which genes control the magnitude of responses, possible endophenotypes, and the potential functions and causes of pathological anxiety states in humans. PUBLIC HEALTH RELEVANCE: The proposed project investigates how anxiety-producing stimuli lead to changes in the behavior of Drosophila melanogaster in a novel open field arena. The studies will produce a foundation for further dissecting the genetic and neural basis of anxiety in both invertebrates and vertebrates.